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Photoacoustic-immune therapy with a multi-purpose black phosphorus-based nanoparticle.

ABSTRACT: Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.

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Supplementary material is available for this article at 10.1007/s12274-020-3028-x and is accessible for authorized users.

SUBMITTER: Zeng F

PROVIDER: S-EPMC7455780 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The 3D printing is described of a complete and portable system comprising a batch injection analysis (BIA) cell and an electrochemical platform with eight sensing electrodes. Both BIA and electrochemical cells were printed within 3.4 h using a multimaterial printer equipped with insulating, flexible, and conductive filaments at cost of ca. ~ U$ 1.2 per unit, and their integration was based on a threadable assembling without commercial component requirements. Printed electrodes were exposed to electrochemical/Fenton pre-treatments to improve the sensitivity. Scanning electron microscopy and electrochemical impedance spectroscopy measurements upon printed materials revealed high-fidelity 3D features (90 to 98%) and fast heterogeneous rate constants ((1.5 ± 0.1) × 10-3 cm s-1). Operational parameters of BIA cell were optimized using a redox probe composed of [Fe(CN)6]4-/3- under stirring and the best analytical performance was achieved using a dispensing rate of 9.0 µL s-1 and an injection volume of 2.0 µL. The proof of concept of the printed device for bioanalytical applications was evaluated using adrenaline (ADR) as target analyte and its redox activities were carefully evaluated through different voltammetric techniques upon multiple 3D-printed electrodes. The coupling of BIA system with amperometric detection ensured fast responses with well-defined peak width related to the oxidation of ADR applying a potential of 0.4 V vs Ag. The fully 3D-printed system provided suitable analytical performance in terms of repeatability and reproducibility (RSD ≤ 6%), linear concentration range (5 to 40 µmol L-1; R2 = 0.99), limit of detection (0.61 µmol L-1), and high analytical frequency (494 ± 13 h-1). Lastly, artificial urine samples were spiked with ADR solutions at three different concentration levels and the obtained recovery values ranged from 87 to 118%, thus demonstrating potentiality for biological fluid analysis. Based on the analytical performance, the complete device fully printed through additive manufacturing technology emerges as powerful, inexpensive, and portable tool for electroanalytical applications involving biologically relevant compounds.

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Photoacoustic-immune therapy with a multi-purpose black phosphorus-based nanoparticle.

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